铅（Pb）暴露个体中miR-148a与DNA甲基化谱之间的关联
Association Between miR-148a and DNA Methylation Profile in Individuals Exposed to Lead (Pb).
作者信息
de Araújo Marília Ladeira, Gomes Bruno Costa, Devóz Paula Pícoli, Duarte Nathália de Assis Aguilar, Ribeiro Diego Luis, de Araújo Adriana Ladeira, Batista Bruno Lemos, Antunes Lusânia Maria Greggi, Barbosa Fernando, Rodrigues António Sebastião, Rueff José, Barcelos Gustavo Rafael Mazzaron
机构信息
Department of Biosciences, Institute of Health and Society, Federal University of São Paulo, Santos, Brazil.
Center for Toxicogenomics and Human Health, NOVA Medical School (NMS), Universidade Nova de Lisboa, Lisbon, Portugal.
出版信息
Front Genet. 2021 Feb 17;12:620744. doi: 10.3389/fgene.2021.620744. eCollection 2021.
Experimental and epidemiologic studies have shown that lead (Pb) is able to induce epigenetic modifications, such as changes in DNA methylation profiles, in chromatin remodeling, as well as the expression of non-coding RNAs (ncRNAs). However, very little is known about the interactions between microRNAs (miRNAs) expression and DNA methylation status in individuals exposed to the metal. The aim of the present study was to investigate the impact of hsa-miR-148a expression on DNA methylation status, in 85 workers exposed to Pb. Blood and plasma lead levels (BLL and PLL, respectively) were determined by ICP-MS; expression of the miRNA-148a was quantified by RT-qPCR (TaqMan assay) and assessment of the global DNA methylation profile (by measurement of 5-methylcytosine; % 5-mC) was performed by ELISA. An inverse association was seen between miR-148a and % 5-mC DNA, as a function of BLL and PLL (β = -3.7; = 0.071 and β = -4.1; = 0.049, respectively) adjusted for age, BMI, smoking, and alcohol consumption. Taken together, our study provides further evidence concerning the interactions between DNA methylation profile and miR-148a, in individuals exposed to Pb.
实验和流行病学研究表明，铅（Pb）能够诱导表观遗传修饰，如DNA甲基化谱的变化、染色质重塑以及非编码RNA（ncRNA）的表达。然而，对于接触该金属的个体中，微小RNA（miRNA）表达与DNA甲基化状态之间的相互作用却知之甚少。本研究的目的是调查85名接触铅的工人中，hsa-miR-148a表达对DNA甲基化状态的影响。通过电感耦合等离子体质谱法（ICP-MS）测定血液和血浆中的铅水平（分别为BLL和PLL）；通过逆转录定量聚合酶链反应（RT-qPCR，TaqMan法）对miRNA-148a的表达进行定量，并通过酶联免疫吸附测定法（ELISA）评估整体DNA甲基化谱（通过测量5-甲基胞嘧啶；% 5-mC）。在校正年龄、体重指数、吸烟和饮酒因素后，发现miR-148a与% 5-mC DNA之间呈负相关，其与BLL和PLL的函数关系分别为（β = -3.7；P = 0.071和β = -4.1；P = 0.049）。综上所述，我们的研究为接触铅的个体中DNA甲基化谱与miR-148a之间的相互作用提供了进一步的证据。
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